Mechanical disruption of the primary tumor using magnetic beads inhibits metastasis of breast cancer. (100.24)

Abstract

Abstract Successful anti-tumor effects are weakened by removal of the tumor antigen pool (i.e. surgery) or use of cytoreductive and immunosuppressive therapies (i.e. chemotherapy and radiation). We hypothesize that mechanical disruption of the tumor in situ will augment immune responses due to antigen release. Iron particles were injected as magneto-rheological fluid (MRF) into an orthotopic primary breast cancer and followed by application of a magnetic field to exert force and shear stress on the tumor. This will result in disruption of the tumor’s architecture and induction of classical “danger signals”: necrotic death, release of tumor antigen with activation of a localized immune response. To promote systemic immune responses we combined MRF treatments with immunotherapy (IT) at suboptimal dosages. Tumors treated with daily application of magnetic field showed increased necrotic cell death, recruitment of activated DCs (i.e. MHC II+, CD83+) to the draining LNs with production of proinflammatory cytokines/chemokines. We then combined MRF treatment with IT to determine if systemic anti-tumor effects could be achieved. Not only have we observed suppression of tumor growth on the contralateral side treated with MRF and IT but also we saw absence of metastasis to the bone marrow of animals treated with either MRF and IT or MRF and magnetic field alone. These data suggest that MRF and magnetic field application to the primary tumor synergize with immunotherapy in disseminated cancer.